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Showing toxin card for Clonidine (T3D2829)

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Version 1.0
Creation Date 2009-07-21 20:27:11
Update Date 2010-05-18 21:00:13
Accession Number T3D2829
Name Clonidine
Compound Type
  • Adrenergic alpha-Agonist
  • Analgesic
  • Antihypertensive Agent
  • Central alpha-Agonist
  • Drug
  • Sympatholytic
Description An alpha-2 adrenergic agonist that crosses the blood-brain barrier. Clonidine acts centrally by reducing sympathetic tone, resulting in a fall in diastolic and systolic blood pressure and a reduction in heart rate. It also acts peripherally, and this peripheral activity may be responsible for the transient increase in blood pressure seen during rapid intravenous administration. (From Martindale, the Extra Pharmacopoeia, 30th ed, p350)
Synonyms
  1. Chlornidinum
  2. Clonidin
  3. Clonidine HCl
  4. Clonidinhydrochlorid
  5. Clonidinum [INN-Latin]
  6. ST 155BS
Chemical IUPAC Name N-(2,6-dichlorophenyl)-4,5-dihydro-1H-imidazol-2-amine
Chemical Formula C9H9Cl2N3
Chemical Structure Structure
CAS Registry Number 4205-90-7
InChI Identifier InChI=1S/C9H9Cl2N3/c10-6-2-1-3-7(11)8(6)14-9-12-4-5-13-9/h1-3H,4-5H2,(H2,12,13,14)
InChI Key InChIKey=GJSURZIOUXUGAL-UHFFFAOYSA-N
PubChem Compound ID 2803 Link Image
KEGG ID C07668 Link Image
UniProt ID Not Available
OMIM ID Not Available
ChEBI ID 46632 Link Image
BioCyc ID Not Available
SuperToxic ID Not Available
CTD ID Not Available
Stitch ID Clonidine Link Image
DrugBank ID DB00575 Link Image
PDB ID Not Available
ACToR ID Not Available
Wikipedia Link http://en.wikipedia.org/wiki/Clonidine Link Image
Monoisotopic Mass 229.017353
MOL File Show
PDB File Show
SDF File Show
SMILES ClC1=CC=CC(Cl)=C1NC1=NCCN1
Appearance Not Available
Melting Point 130oC
Solubility Appreciable
Predicted LogP 2.4851
Route of Exposure Oral
Mechanism of Action Clonidine acts as an agonist at presynaptic alpha(2)-receptors in the nucleus tractus solitarius of the medulla oblongata. Stimulation of these receptors results in the supression of efferent sympathetic pathways and the subsequent decrease in blood pressure and vascular tone in the heart, kidneys, and peripheral vasculature. Clonidine is also a partial agonist at presynaptic alpha(2)-adrenergic receptors of peripheral nerves in vascular smooth muscle.
Metabolism Hepatic. Metabolized through minor pathways. The major metabolite, p-hydroxyclonidine, is present in concentrations less than 10% of those of unchanged clonidine in urine.
Toxicity Values LD50: 150 mg/kg (oral, rat) LD50: 30 mg/kg (oral, dog)
Lethal Dose Not Available
Carcinogenicity (IARC Classification) Not Available
Uses/Sources Not Available
Minimum Risk Level Not Available
Health Effects Not Available
Symptoms Symptoms of overdose include constriction of pupils of the eye, drowsiness, high blood pressure followed by a drop in pressure, irritability, low body temperature, slowed breathing, slowed heartbeat, slowed reflexes, and weakness.
Treatment There is no specific antidote for clonidine overdosage. Clonidine overdosage may result in the rapid development of CNS depression; therefore, induction of vomiting with ipecac syrup is not recommended. Gastric lavage may be indicated following recent and/or large ingestions. Administration of activated charcoal and/or a cathartic may be beneficial. Supportive care may include atropine sulfate for bradycardia, intravenous fluids and/or vasopressor agents for hypotension and vasodilators for hypertension. Naloxone may be a useful adjunct for the management of clonidine-induced respiratory depression, hypotension and/or coma; blood pressure should be monitored since the administration of naloxone has occasionally resulted in paradoxical hypertension. Tolazoline administration has yielded inconsistent results and is not recommended as first-line therapy. (V650)
General References
  • T948 - Drugs.com
  • T950 - Hossmann V, Maling TJ, Hamilton CA, Reid JL, Dollery CT: Sedative and cardiovascular effects of clonidine and nitrazepam. Clin Pharmacol Ther. 1980 Aug;28(2):167-76. [PubMed Link Image]
  • T949 - Schapiro NA: "Dude, you don't have Tourette's:" Tourette's syndrome, beyond the tics. Pediatr Nurs. 2002 May-Jun;28(3):243-6, 249-53. [PubMed Link Image]
Targets
  1. Alpha-2A adrenergic receptor
  2. Substance-K receptor
Target 1 [top]
Target 1 ID 1143
Target 1 Name Alpha-2A adrenergic receptor
Target 1 Mechanism of Action Clonidine acts as an agonist at presynaptic alpha(2)-receptors in the nucleus tractus solitarius of the medulla oblongata. Stimulation of these receptors results in the supression of efferent sympathetic pathways and the subsequent decrease in blood pressure and vascular tone in the heart, kidneys, and peripheral vasculature. Clonidine is also a partial agonist at presynaptic alpha(2)-adrenergic receptors of peripheral nerves in vascular smooth muscle.
Target 1 Description Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol
Target 1 Synonyms
  1. Alpha-2A adrenoreceptor; Alpha-2A adrenoceptor; Alpha-2AAR; Alpha-2 adrenergic receptor subtype C10
Target 1 Gene Name ADRA2A
Target 1 Protein Sequence >Alpha-2A adrenergic receptor 
MGSLQPDAGNASWNGTEAPGGGARATPYSLQVTLTLVCLAGLLMLLTVFGNVLVIIAVFT
SRALKAPQNLFLVSLASADILVATLVIPFSLANEVMGYWYFGKAWCEIYLALDVLFCTSS
IVHLCAISLDRYWSITQAIEYNLKRTPRRIKAIIITVWVISAVISFPPLISIEKKGGGGG
PQPAEPRCEINDQKWYVISSCIGSFFAPCLIMILVYVRIYQIAKRRTRVPPSRRGPDAVA
APPGGTERRPNGLGPERSAGPGGAEAEPLPTQLNGAPGEPAPAGPRDTDALDLEESSSSD
HAERPPGPRRPERGPRGKGKARASQVKPGDSLPRRGPGATGIGTPAAGPGEERVGAAKAS
RWRGRQNREKRFTFVLAVVIGVFVVCWFPFFFTYTLTAVGCSVPRTLFKFFFWFGYCNSS
LNPVIYTIFNHDFRRAFKKILCRGDRKRIV
Target 1 Number of Residues 450
Target 1 Molecular Weight 48956.3
Target 1 Theoretical pI 10.20
Target 1 GO Classification
Function
amine receptor activity
adrenoceptor activity
alpha-adrenergic receptor activity
alpha2-adrenergic receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
cell
membrane
intrinsic to membrane
integral to membrane
Target 1 General Function Involved in alpha2-adrenergic receptor activity
Target 1 Pathways Not Available
Target 1 Reactions Not Available
Target 1 Signals
  • None
Target 1 Transmembrane Regions
  • 34-59
  • 71-96
  • 107-129
  • 152-172
  • 195-217
  • 375-395
  • 410-429
Target 1 Essentiality Non Essential
Target 1 Domain Function PF00001:7tm_1
Target 1 GenBank ID Protein Not Available
Target 1 UniProtKB ID P08913 Link Image
Target 1 Cellular Location Cell membrane
Target 1 Gene Sequence >1353 bp 
ATGGGCTCCCTGCAGCCGGACGCGGGCAACGCGAGCTGGAACGGGACCGAGGCGCCGGGG
GGCGGCGCCCGGGCCACCCCTTACTCCCTGCAGGTGACGCTGACGCTGGTGTGCCTGGCC
GGCCTGCTCATGCTGCTCACCGTGTTCGGCAACGTGCTCGTCATCATCGCCGTGTTCACG
AGCCGCGCGCTCAAGGCGCCCCAAAACCTCTTCCTGGTGTCTCTGGCCTCGGCCGACATC
CTGGTGGCCACGCTCGTCATCCCTTTCTCGCTGGCCAACGAGGTCATGGGCTACTGGTAC
TTCGGCAAGGCTTGGTGCGAGATCTACCTGGCGCTCGACGTGCTCTTCTGCACGTCGTCC
ATCGTGCACCTGTGCGCCATCAGCCTGGACCGCTACTGGTCCATCACACAGGCCATCGAG
TACAACCTGAAGCGCACGCCGCGCCGCATCAAGGCCATCATCATCACCGTGTGGGTCATC
TCGGCCGTCATCTCCTTCCCGCCGCTCATCTCCATCGAGAAGAAGGGCGGCGGCGGCGGC
CCGCAGCCGGCCGAGCCGCGCTGCGAGATCAACGACCAGAAGTGGTACGTCATCTCGTCG
TGCATCGGCTCCTTCTTCGCTCCCTGCCTCATCATGATCCTGGTCTACGTGCGCATCTAC
CAGATCGCCAAGCGTCGCACCCGCGTGCCACCCAGCCGCCGGGGTCCGGACGCCGTCGCC
GCGCCGCCGGGGGGCACCGAGCGCAGGCCCAACGGTCTGGGCCCCGAGCGCAGCGCGGGC
CCGGGGGGCGCAGAGGCCGAACCGCTGCCCACCCAGCTCAACGGCGCCCCTGGCGAGCCC
GCGCCGGCCGGGCCGCGCGACACCGACGCGCTGGACCTGGAGGAGAGCTCGTCTTCCGAC
CACGCCGAGCGGCCTCCAGGGCCCCGCAGACCCGAGCGCGGTCCCCGGGGCAAAGGCAAG
GCCCGAGCGAGCCAGGTGAAGCCGGGCGACAGCCTGCCGCGGCGCGGGCCGGGGGCGACG
GGGATCGGGACGCCGGCTGCAGGGCCGGGGGAGGAGCGCGTCGGGGCTGCCAAGGCGTCG
CGCTGGCGCGGGCGGCAGAACCGCGAGAAGCGCTTCACGTTCGTGCTGGCCGTGGTCATC
GGAGTGTTCGTGGTGTGCTGGTTCCCCTTCTTCTTCACCTACACGCTCACGGCCGTCGGG
TGCTCCGTGCCACGCACGCTCTTCAAATTCTTCTTCTGGTTCGGCTACTGCAACAGCTCG
TTGAACCCGGTCATCTACACCATCTTCAACCACGATTTCCGCCGCGCCTTCAAGAAGATC
CTCTGTCGGGGGGACAGGAAGCGGATCGTGTGA
Target 1 GenBank Gene ID Not Available
Target 1 GeneCard ID ADRA2A Link Image
Target 1 GenAtlas ID ADRA2A Link Image
Target 1 HGNC ID HGNC:281 Link Image
Target 1 Chromosome Location Chromosome:10
Target 1 Locus 10q24-q26
Target 1 SNPs SNPJam Report Link Image
Target 1 Toxin References
  • T951 - Fairbanks CA, Stone LS, Kitto KF, Nguyen HO, Posthumus IJ, Wilcox GL: alpha(2C)-Adrenergic receptors mediate spinal analgesia and adrenergic-opioid synergy. J Pharmacol Exp Ther. 2002 Jan;300(1):282-90. [PubMed Link Image]
  • T953 - Lavand'homme PM, Ma W, De Kock M, Eisenach JC: Perineural alpha(2A)-adrenoceptor activation inhibits spinal cord neuroplasticity and tactile allodynia after nerve injury. Anesthesiology. 2002 Oct;97(4):972-80. [PubMed Link Image]
  • T560 - Ozdogan UK, Lahdesmaki J, Mansikka H, Scheinin M: Loss of amitriptyline analgesia in alpha 2A-adrenoceptor deficient mice. Eur J Pharmacol. 2004 Feb 6;485(1-3):193-6. [PubMed Link Image]
  • T952 - Wang XM, Zhang ZJ, Bains R, Mokha SS: Effect of antisense knock-down of alpha(2a)- and alpha(2c)-adrenoceptors on the antinociceptive action of clonidine on trigeminal nociception in the rat. Pain. 2002 Jul;98(1-2):27-35. [PubMed Link Image]
  • T954 - Ozdogan UK, Lahdesmaki J, Hakala K, Scheinin M: The involvement of alpha 2A-adrenoceptors in morphine analgesia, tolerance and withdrawal in mice. Eur J Pharmacol. 2004 Aug 23;497(2):161-71. [PubMed Link Image]
Target 1 General References 2823383; 2568356; 2170371; 10948191; 16567612
Target 2 [top]
Target 2 ID 967
Target 2 Name Substance-K receptor
Target 2 Mechanism of Action Clonidine acts as an agonist at presynaptic alpha(2)-receptors in the nucleus tractus solitarius of the medulla oblongata. Stimulation of these receptors results in the supression of efferent sympathetic pathways and the subsequent decrease in blood pressure and vascular tone in the heart, kidneys, and peripheral vasculature. Clonidine is also a partial agonist at presynaptic alpha(2)-adrenergic receptors of peripheral nerves in vascular smooth muscle.
Target 2 Description This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system
Target 2 Synonyms
  1. SKR; Neurokinin A receptor; NK-2 receptor; NK-2R; Tachykinin receptor 2
Target 2 Gene Name TACR2
Target 2 Protein Sequence >Substance-K receptor 
MGTCDIVTEANISSGPESNTTGITAFSMPSWQLALWATAYLALVLVAVTGNAIVIWIILA
HRRMRTVTNYFIVNLALADLCMAAFNAAFNFVYASHNIWYFGRAFCYFQNLFPITAMFVS
IYSMTAIAADRYMAIVHPFQPRLSAPSTKAVIAGIWLVALALASPQCFYSTVTMDQGATK
CVVAWPEDSGGKTLLLYHLVVIALIYFLPLAVMFVAYSVIGLTLWRRAVPGHQAHGANLR
HLQAMKKFVKTMVLVVLTFAICWLPYHLYFILGSFQEDIYCHKFIQQVYLALFWLAMSST
MYNPIIYCCLNHRFRSGFRLAFRCCPWVTPTKEDKLELTPTTSLSTRVNRCHTKETLFMA
GDTAPSEATSGEAGRPQDGSGLWFGYGLLAPTKTHVEI
Target 2 Number of Residues 398
Target 2 Molecular Weight 44441.7
Target 2 Theoretical pI 8.63
Target 2 GO Classification
Function
peptide receptor activity, G-protein coupled
neuropeptide receptor activity
tachykinin receptor activity
signal transducer activity
receptor activity
transmembrane receptor activity
G-protein coupled receptor activity
rhodopsin-like receptor activity
Process
cellular process
cell communication
signal transduction
cell surface receptor linked signal transduction
G-protein coupled receptor protein signaling pathway
Component
plasma membrane
cell
membrane
intrinsic to membrane
integral to membrane
Target 2 General Function Involved in tachykinin receptor activity
Target 2 Pathways Not Available
Target 2 Reactions Not Available
Target 2 Signals
  • None
Target 2 Transmembrane Regions
  • 33-56
  • 70-90
  • 108-129
  • 150-170
  • 197-218
  • 252-272
  • 291-310
Target 2 Essentiality Non Essential
Target 2 Domain Function PF00001:7tm_1
Target 2 GenBank ID Protein Not Available
Target 2 UniProtKB ID P21452 Link Image
Target 2 Cellular Location Cell membrane
Target 2 Gene Sequence Not Available
Target 2 GenBank Gene ID Not Available
Target 2 GeneCard ID TACR2 Link Image
Target 2 GenAtlas ID TACR2 Link Image
Target 2 HGNC ID HGNC:11527 Link Image
Target 2 Chromosome Location Chromosome:10
Target 2 Locus 10q11-q21
Target 2 SNPs SNPJam Report Link Image
Target 2 Toxin References
  • S918 - Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed Link Image]
Target 2 General References 2173708; 1845990; 1710456; 1659296; 1848773

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